Caries continues to be a prevalent disease with high incidence among all age groups. Ammonia production from the hydrolysis of arginine and urea by enzymes of oral bacteria moderates plaque acidification and may inhibit dental caries, as suggested by in vitro studies and indirect clinical observations. The objective of this study is to examine the relationship of arginine deiminase (AD) and urease activities with dental caries status at the clinical level. We hypothesize that AD and urease activities in plaque and/or saliva of caries free subjects is significantly higher than in caries active subjects. AD and urease activities will be measured in dental plaque and saliva samples from caries free subjects, caries experienced subjects, and subjects with at least 4 teeth with active caries. Specific Aim (SA) 1 will determine the magnitude and the direction of the association between plaque and saliva AD and urease activity levels with dental caries in human subjects. SA 2 will examine the relationship between AD and urease activity levels with the numbers of selected major acid-producing and alkali-producing bacterial species in the oral samples. SA 3 will investigate the predictors of AD and urease activity levels. SA 1 will be met through a case-control study and SA 2 will be met using a sub-sample of the subjects (10 with the highest, 10 with the lowest, and 10 with medium plaque AD and urease levels). SA3 will be met by gathering information on patient's age, gender, race, dental history, plaque, and frequency of oral care, and investigating the relationship of these explanatory factors to AD and urease activity levels in plaque and saliva. If the results of the present study support an association between AD and/or urease activity levels with dental caries in adults, the knowledge obtained will be applied to the design of a prospective cohort study at the end of the grant period, which will determine whether this association is a cause-and-effect one. If AD and urease activity levels are shown to be predictive of caries risk in adults, either alone or in combination with other risk factors, we will then apply this relationship to the development of novel approaches for early identification of individuals at risk to develop caries and for caries prevention strategies. PUBLIC HEALTH RELEVANCE: The proposed study will contribute to the development of novel methods for caries risk assessment and prevention, while providing a better understanding of unknown factors affecting caries risk.